Oncopeptidomics: A Useful Approach for Cancer Diagnosis?

In this issue of Clinical Chemistry , Mary Lopez and colleagues (1) describe novel methods for isolation of protein-bound peptides from serum and their characterization by mass spectrometry. Lopez et al. used selected peptide combinations to develop a new profiling method for ovarian cancer diagnosis. To put this advance into perspective, I will briefly summarize relevant previous literature on diagnostic applications of serum proteomic and peptidomic profiling by mass spectrometry.Approximately 5 years ago, a new approach for diagnosing ovarian cancer, by use of SELDI-TOF mass spectrometry, was proposed by the coauthors of the article under discussion (2). It was then hypothesized that proteins or protein fragments released by tumor cells or their microenvironment may enter the general circulation. By the use of a SELDI chip, proteins or peptides could be extracted from crude serum and used for diagnostic purposes with the aid of mass spectrometry and a mathematical algorithm. Similar methods have subsequently been used to diagnose numerous other malignancies, such as breast, prostate, bladder, pancreatic, head and neck, lung, liver, and nasopharyngeal cancers, as well as gliomas and melanomas, with impressive diagnostic sensitivities and specificities. This method has enjoyed ample coverage in scientific journals, the media, and international conferences (3).This author and others have criticized this diagnostic approach for methodological shortcomings and bioinformatic artifacts (4)(5)(6)(7)(8)(9). During the last 5 years, healthy debates have been conducted in journals (including this one) and at conferences (10)(11). An independent validation study would be the best test for this technology. As yet, however, no published validation is available to confirm that these methodologies are working. The proponents of the serum proteomic profiling methods for cancer diagnostics have now turned their attention to another possibility, proposing to interrogate the …